Herpes zoster (HZ), or shingles, is a painful vesicular rash, usually unilateral, caused by the varicella zoster virus (VZV). The pain associated with HZ can be debilitating, with a serious impact on quality of life, and the economic costs of managing the disease represent an important burden on both health services and society. Approximately 30% of people will develop HZ at some point during their life. In raw numbers, approximately 1 million people in the United States are affected with HZ every year. In 2006, zoster vaccine received Food and Drug Administration (FDA) approval for use in healthy adults aged 60 and older. Because zoster and its attendant neurologic complication of postherpetic neuralgia (PHN) are common and serious among the elderly, it seems prudent to recommend zoster vaccine. The potential impact of vaccination on the burden of the disease in this population is significant. Despite the development of a vaccine to prevent zoster, about only 2- 7% of the eligible US population was vaccinated during 2007-2008. Concerns over the safety of the vaccine, both on the part of vaccines and their providers, might explain this low uptake. In addition, even if every healthy adult in the United States over age 60 years is vaccinated, there would still be approximately 500,000 zoster cases annually. The results of this study will advance the understanding of not only the safety of the zoster vaccine but also the risk factors for vaccine failure and development of PHN modified by vaccination and ultimately inform vaccination recommendations. The aims of the study are to determine the incidence of reactivation of Oka strain VZV in community-dwelling persons vaccinated with zoster vaccines;to test clinical isolates for evidence of recombination between vaccine and wild-type strains VZV;to identify risk factors of HZ among individuals vaccinated with zoster vaccines;to identify risk factors for post-herpetic neuralgia (PHN) among HZ cases who were either vaccinated or unvaccinated with zoster vaccines, and to compare the clinical manifestations and risk of PHN between vaccinated and unvaccinated individuals. This proposed research will be conducted among a cohort of persons aged 60 years or older who are members of Kaiser Permanente Southern California (KPSC). The cohort of those vaccinated with a zoster vaccine and an unvaccinated comparison cohort will be assembled by the clinical research infrastructure at KPSC, resulting in one of the largest Zostavax vaccinated cohorts in the country. Through partnership with the National VZV Lab in the Centers for Disease Control and Prevention (CDC) and Columbia University, we will provide critical information about the potential role of reactivation of vaccine strain Oka VZV in a community-dwelling population without the selection factors inherent in clinical trial settings. Moreover, the insights about risk factors and sequelae of VZV reactivation and PHN will inform vaccination recommendations. PUBLIC HEALTH RELEVANCE: In 2006, zoster vaccine received Food and Drug Administration (FDA) approval for use in healthy adults aged 60 and older. Zoster vaccine increases cell-mediated immunity to VZV in such individuals, and the boost is likely to last for decades. Because zoster and its attendant neurologic complication of postherpetic neuralgia (PHN) are common and serious among the elderly, it seems prudent to recommend zoster vaccine. The potential impact of vaccination on the burden of the disease in this population is significant. Despite the development of a vaccine to prevent zoster, about only 2-7% of the eligible US population were vaccinated during 2007-2008. Concerns over the safety of the vaccine, both on the part of vaccines and their providers, might explain this low uptake. In addition, even if every healthy adult in the United States over age 60 years is vaccinated, there would still be approximately 500,000 zoster cases annually. The results of this study will advance the understanding of not only the safety of the zoster vaccine but also the risk factors for vaccine failure and development of PHN modified by vaccination and ultimately inform vaccination recommendations.